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https://www.readbyqxmd.com/read/28943409/interleukin-1-%C3%AE-induced-smad2-3-linker-modifications-are-tak1-dependent-and-delay-tgf%C3%AE-signaling-in-primary-human-mesenchymal-stem-cells
#1
Guus G van den Akker, Henk M van Beuningen, Elly L Vitters, Marije I Koenders, Fons A de Loo, Peter L van Lent, Esmeralda N Blaney Davidson, Peter M van der Kraan
BACKGROUND: Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFβ) signaling. TGFβ binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 β (IL1β) on SMAD2/3 signaling dynamics and post-translational modifications...
September 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28941865/effect-of-curcumin-on-acute-spinal-cord-injury-in-mice-via-inhibition-of-inflammation-and-tak1-pathway
#2
Nanwen Zhang, Guicai Wei, Jian Ye, Lin Yang, Yunda Hong, Guisheng Liu, Huifen Zhong, Xinyi Cai
BACKGROUND: Traumatic spinal cord injury (SCI) is damage to the spinal cord that results in damaged spinal cord function. As a natural compound, curcumin has recently been shown to have anti-inflammatory and strong antioxidant activities. To investigate the effect of curcumin against acute spinal cord injury (SCI), we explored its induced effects in SCI mice. Transforming growth factor (TGF)-activated kinase 1 (TAK1) is a member of the MAPKKK family and plays an essential role in TNF, IL-1, and Toll-like receptor (TLR) signaling pathways...
February 14, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28924041/irak4-kinase-activity-controls-toll-like-receptor-induced-inflammation-through-the-transcription-factor-irf5-in-primary-human-monocytes
#3
Leah Cushing, Aaron Winkler, Scott A Jelinsky, Katherine Lee, Wouter Korver, Rachael Hawtin, Vikram R Rao, Margaret Fleming, Lih-Ling Lin
Interleukin-1 receptor associated kinase 4 (IRAK4) plays a critical role in innate immune signaling by Toll-like receptors (TLRs), and loss of IRAK4 activity in mice and humans increases susceptibility to bacterial infections and causes defects in TLR and IL1 ligand sensing. However, the mechanism by which IRAK4 activity regulates the production of downstream inflammatory cytokines is unclear. Using transcriptomic and biochemical analyses of human monocytes treated with a highly potent and selective inhibitor of IRAK4, we show that IRAK4 kinase activity controls the activation of the transcription factor IRF5, a transcription factor implicated in the pathogenesis of multiple autoimmune diseases...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912140/down-regulation-of-safb-sustains-the-nf-%C3%AE%C2%BAb-pathway-by-targeting-tak1-during-the-progression-of-colorectal-cancer
#4
Hong-Li Jiao, Ya-Ping Ye, Run-Wei Yang, Hui-Ying Sun, Shu-Yang Wang, Yong-Xia Wang, Zhi-Yuan Xiao, Liu-Qing He, Juan-Juan Cai, Wen-Ting Wei, Yan-Ru Chen, Chun-Cai Gu, Yue-Long Cai, Yun-Teng Hu, Qiu-Hua Lai, Jun-Feng Qiu, Li Liang, Guangwen Cao, Wen-Ting Liao, Yanqing Ding
PURPOSE: To investigate the role and the underlying mechanism of scaffold attachment factor B (SAFB) in the progression of colorectal cancer (CRC). EXPERIMENTAL DESIGN: SAFB expression was analyzed in the Cancer Outlier Profile Analysis of Oncomine and in 175 paraffin-embedded archived CRC tissues. Gene Ontology analyses were performed to explore the mechanism of SAFB in CRC progression. Western blot, RT-PCR, luciferase assay and chromatin immunoprecipitation (ChIP) were used to detect the regulation of transforming growth factor-β-activated kinase 1 (TAK1) and NF-κB signaling by SAFB...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28906490/popx2-phosphatase-regulates-apoptosis-through-the-tak1-ikk-nf-%C3%AE%C2%BAb-pathway
#5
Ting Weng, Cheng-Gee Koh
Chemoresistance is one of the leading causes that contributes to tumor relapse and poor patient outcome after several rounds of drug therapy. The causes of chemoresistance are multi-factorial. Ultimately, it is the balance of pro- and anti-apoptotic activities in the cells. We have previously reported links between POPX2 serine/threonine phosphatase with cell motility and invasiveness of breast cancer cells. Here, we show that POPX2 plays a role in the regulation of apoptosis. The effect of POPX2 on apoptosis centers on the inactivation of TGF-β activated kinase (TAK1)...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28891811/nf-%C3%AE%C2%BAb-regulates-gdf-15-to-suppress-macrophage-surveillance-during-early-tumor-development
#6
Nivedita M Ratnam, Jennifer M Peterson, Erin E Talbert, Katherine J Ladner, Priyani V Rajasekera, Carl R Schmidt, Mary E Dillhoff, Benjamin J Swanson, Ericka Haverick, Raleigh D Kladney, Terence M Williams, Gustavo W Leone, David J Wang, Denis C Guttridge
Macrophages are attracted to developing tumors and can participate in immune surveillance to eliminate neoplastic cells. In response, neoplastic cells utilize NF-κB to suppress this killing activity, but the mechanisms underlying their self-protection remain unclear. Here, we report that this dynamic interaction between tumor cells and macrophages is integrally linked by a soluble factor identified as growth and differentiation factor 15 (GDF-15). In vitro, tumor-derived GDF-15 signals in macrophages to suppress their proapoptotic activity by inhibiting TNF and nitric oxide (NO) production...
September 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28887166/dusp14-protects-against-hepatic-ischemia-reperfusion-injury-via-tak1-suppression
#7
Xiaozhan Wang, Wenzhe Mao, Chun Fang, Song Tian, Xueyong Zhu, Ling Yang, Zan Huang, Hongliang Li
BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (I/R) injury is characterized by severe inflammation and extensive cell death. Multiple signaling pathways, including NF-κB and MAPK/Jnk, play important roles in this process. Identifying the unknown critical regulators of these signaling pathways may provide potential targets for therapeutic application. Dual specific phosphatase 14 (DUSP14) acts as a negative regulator of NF-κB signaling. However, the function of Dusp14 in hepatic I/R injury remains unknown...
September 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28875549/the-contribution-of-toll-like-receptor-signaling-to-the-development-of-liver-fibrosis-and-cancer-in-hepatocyte-specific-tak1-deleted-mice
#8
Isabelle Jingyi Song, Yoon Mee Yang, Sayaka Inokuchi-Shimizu, Yoon Seok Roh, Ling Yang, Ekihiro Seki
Hepatocyte death is associated with liver inflammation, fibrosis, and hepatocellular carcinoma (HCC). Damaged cells trigger inflammation through activation of Toll-like receptor (TLR). Although the role of TLR4 in HCC development has been reported, the role of TLR9 in the development of HCC remains elusive. To investigate the role of TLR4 and TLR9 signaling in liver inflammation-fibrosis-cancer axis, we took advantage of mice with hepatic deletion of transforming growth factor-β-activated kinase 1 (Tak1ΔHep) that develop spontaneous liver injury, inflammation, fibrosis, and HCC, recapitulating the pathology of human HCC...
September 5, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28874783/hyperactive-tgf-%C3%AE-signaling-in-smooth-muscle-cells-exposed-to-hiv-protein-s-and-cocaine-role-in-pulmonary-vasculopathy
#9
Pranjali Dalvi, Himanshu Sharma, Tomara Konstantinova, Miles Sanderson, Amy O' Brien-Ladner, Navneet K Dhillon
We earlier demonstrated synergistic increase in the proliferation of pulmonary smooth muscle cells on exposure to HIV-proteins and/or cocaine due to severe down-modulation of bone morphogenetic protein receptor (BMPR) axis: the anti-proliferative arm of TGF-β super family of receptors. Here, now we demonstrate the effect of HIV-Tat and cocaine on the proliferative TGF-β signaling cascade. We observed a significant increase in the secretion of TGF-β1 ligand along with enhanced protein expression of TGFβ Receptor (TGFβR)-1, TGFβR-2 and phosphorylated SMAD2/3 in human pulmonary arterial smooth muscle cells on treatment with cocaine and Tat...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872665/expression-of-human-cathelicidin-peptide-ll-37-in-inflammatory-bowel-disease
#10
Shoko Kusaka, Atsushi Nishida, Kenichiro Takahashi, Shigeki Bamba, Hiroyuki Yasui, Masahiro Kawahara, Osamu Inatomi, Mitsushige Sugimoto, Akira Andoh
Cathelicidin peptide LL-37 plays an important role in the early host response against invading pathogens via its broad-spectrum antimicrobial activity. In this study, we investigated LL-37 expression in the inflamed mucosa of IBD patients. Furthermore, the regulatory mechanism of LL-37 induction was investigated in human colonic subepithelial myofibroblasts (SEMFs). LL-37 mRNA expression and protein secretion were analyzed using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively...
September 5, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28859670/selective-suppression-of-the-jnk-mmp2-9-signal-pathway-by-tetramethylpyrazine-attenuates-neuropathic-pain-in-rats
#11
Lai Jiang, Cai-Long Pan, Chao-Yu Wang, Bing-Qian Liu, Yuan Han, Liang Hu, Lei Liu, Yang Yang, Jun-Wei Qu, Wen-Tao Liu
BACKGROUND: Activated astrocytes release matrix metalloproteinase-2/9 (MMP-2/9) to induce central sensitization and maintain neuropathic pain. However, the mechanisms involved in the activation of MMP-2/9 on astrocytes during pain remain poorly understood. Meanwhile, there is a lack of effective treatment to inhibit the activation of MMP-2/9 on astrocytes. In this study, we aim to investigate the effect of tetramethylpyrazine (TMP), a natural compound with analgesic effects but unknown mechanisms, on MMP-2/9 in neuropathic pain...
August 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28844021/tlr2-tlr3-and-tlr5-regulation-of-pro-inflammatory-and-pro-labour-mediators-in-human-primary-myometrial-cells
#12
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth continues to be a significant global health care issue, due to our lack of understanding of the mechanisms that drive human labour and delivery. Toll-like receptors (TLRs) are essential in triggering an inflammatory response in human gestational tissues, leading to the production of pro-inflammatory and pro-labour mediators, and thus preterm birth. The aims of this study were to determine whether the adaptor molecules associated with TLR2, TLR3 and TLR5 signalling are involved in human myometrium...
August 24, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28842570/regulation-of-ripk1-activation-by-tak1-mediated-phosphorylation-dictates-apoptosis-and-necroptosis
#13
Jiefei Geng, Yasushi Ito, Linyu Shi, Palak Amin, Jiachen Chu, Amanda Tomie Ouchida, Adnan Kasim Mookhtiar, Heng Zhao, Daichao Xu, Bing Shan, Ayaz Najafov, Guangping Gao, Shizuo Akira, Junying Yuan
Stimulation of TNFR1 by TNFα can promote three distinct alternative mechanisms of cell death: necroptosis, RIPK1-independent and -dependent apoptosis. How cells decide which way to die is unclear. Here, we report that TNFα-induced phosphorylation of RIPK1 in the intermediate domain by TAK1 plays a key role in regulating this critical decision. Using phospho-Ser321 as a marker, we show that the transient phosphorylation of RIPK1 intermediate domain induced by TNFα leads to RIPK1-independent apoptosis when NF-κB activation is inhibited by cycloheximide...
August 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28829887/correlation-analysis-of-adamts-4-vcam-1-and-tak1-expression-in-cartilage-tissue-from-spine-tuberculosis
#14
Z X Qiu, Z S Sha, X M Che, M Y Wang
A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) can effectively degrade articular cartilage matrix proteoglycan and damage the intervertebral disc of spinal tuberculosis patients, resulting in deterioration of the physical properties of articular cartilage. Transforming growth factor β activated kinase 1 (TAK1) is similar to vascular cell adhesion molecule 1 (VCAM-1) and closely related to a variety of pathophysiological processes. This study intended to explore the expression of ADAMTS-4, VCAM-1, and TAK1 in cartilage tissue obtained from spinal tuberculosis patients and their inter-relationships, aiming to provide new treatment approaches for spinal tuberculosis...
August 17, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28827540/the-us2-gene-product-of-herpes-simplex-virus-2-modulates-nf-%C3%AE%C2%BAb-activation-by-targeting-tak1
#15
Xuan Lu, Changjing Huang, Yi Zhang, Yong Lin, Xueyu Wang, Qian Li, Shi Liu, Jingfeng Tang, Li Zhou
HSV-2 is one of the most common sexually transmitted pathogens worldwide and HSV-2 infection triggers cytokine and chemokine production. However, little is known about which HSV-2 genes engage in the regulation of NF-κB signaling and what mechanisms are involved. In a screen of the unique short (Us) regions of HSV-2, we observed that HSV-2 Us2 activates NF-κB signaling. We additionally indicated that deficiencies of Us2 decrease HSV-2 WT mediated NF-κB activation and cytokine and chemokine production, and overexpression of Us2 showed opposite effects...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821620/arjunolic-acid-a-peroxisome-proliferator-activated-receptor-alpha-agonist-regresses-cardiac-fibrosis-by-inhibiting-non-canonical-tgf-%C3%AE-signaling
#16
Trisha Bansal, Emeli Chatterjee, Jasdeep Singh, Arjun Ray, Bishwajit Kundu, V Thankamani, Shantanu Sengupta, Sagartirtha Sarkar
Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant Terminalia arjuna which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive T. arjuna compound, arjunolic acid (AA) in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28820959/takinib-a-selective-tak1-inhibitor-broadens-the-therapeutic-efficacy-of-tnf-%C3%AE-inhibition-for-cancer-and-autoimmune-disease
#17
Juliane Totzke, Deepak Gurbani, Rene Raphemot, Philip F Hughes, Khaldon Bodoor, David A Carlson, David R Loiselle, Asim K Bera, Liesl S Eibschutz, Marisha M Perkins, Amber L Eubanks, Phillip L Campbell, David A Fox, Kenneth D Westover, Timothy A J Haystead, Emily R Derbyshire
Tumor necrosis factor alpha (TNF-α) has both positive and negative roles in human disease. In certain cancers, TNF-α is infused locally to promote tumor regression, but dose-limiting inflammatory effects limit broader utility. In autoimmune disease, anti-TNF-α antibodies control inflammation in most patients, but these benefits are offset during chronic treatment. TAK1 acts as a key mediator between survival and cell death in TNF-α-mediated signaling. Here, we describe Takinib, a potent and selective TAK1 inhibitor that induces apoptosis following TNF-α stimulation in cell models of rheumatoid arthritis and metastatic breast cancer...
August 17, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28819003/skeletal-muscle-signaling-metabolism-and-performance-during-sprint-exercise-in-severe-acute-hypoxia-after-the-ingestion-of-antioxidants
#18
David Morales-Alamo, Borja Guerra, Jesus Gustavo Ponce-Gonzalez, Amelia Guadalupe-Grau, Alfredo Santana, Marcos Martin-Rincon, Miriam Gelabert-Rebato, Joan Aureli Cadefau, Roser Cussó, Cecilia Dorado, Jose A L Calbet
The aim of this study was to determine reactive oxygen species (ROS) could play a role in blunting Thr(172)-AMPKα phosphorylation in human skeletal muscle after sprint exercise in hypoxia and to elucidate the potential signaling mechanisms responsible for this response. Nine volunteers performed a single 30s sprint (Wingate test) in two occasions while breathing hypoxic gas (PIO2=75 mmHg): one after the ingestion of placebo (P) and another following the intake of antioxidants (A) (α-lipoic acid, vitamin C, and vitamin E), with a randomized double-blind design...
August 17, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28817116/total-tanshinones-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization-via-the-myd88-pathway
#19
Hongwei Gao, Xin Liu, Wen Sun, Naixin Kang, Yanli Liu, Shilin Yang, Qiong-Ming Xu, Chunming Wang, Xiuping Chen
Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-α, IL-6, and IL-1β in RAW264...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28811826/anti-inflammatory-effect-of-piper-attenuatum-methanol-extract-in-lps-stimulated-inflammatory-responses
#20
You Jin Kim, Jeong Deok, Sunggyu Kim, Deok Hyo Yoon, Gi-Ho Sung, Adithan Aravinthan, Seungihm Lee, Mi-Nam Lee, Suntaek Hong, Jong-Hoon Kim, Young-Jin Son, Jae Youl Cho
Piper attenuatum is used as a traditional medicinal plant in India. One of the substances in P. attenuatum has been suggested to have anti-inflammatory effects. However, there is insufficient research about the anti-inflammatory mechanisms of action of P. attenuatum. The effects of P. attenuatum methanol extract (Pa-ME) on the production of inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), the expression of proinflammatory genes, the translocation level of transcription factors, and intracellular signaling activities were investigated using macrophages...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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